Medical hypothesis discovery and innovation in ophthalmology

Background: Dry eye disease is a multifactorial ocular-surface disorder. Tobacco smoke exposure has been associated with ocular discomfort and altered tear-film measures, although findings remain inconsistent. This study compared dry-eye symptoms and ocular-surface signs between tobacco smoke-exposed and non-exposed participants.
Methods: This cross-sectional reanalysis used a retrospective, de-identified dataset collected in Gaza in 2023. The sample comprised 81 participants: 40 tobacco smoke-exposed and 41 non-exposed controls. Exposure was defined by a pooled self-reported binary item encompassing cigarette smoking, shisha use, passive smoke exposure, or combinations thereof. Arab Ocular Surface Disease Index (Arab-OSDI) score was the primary outcome; tear break-up time (TBUT), Schirmer I test with topical anesthesia (STT), and corneal fluorescein staining (CFS) were secondary outcomes. All 81 records were analyzed with adjustment for sex and age category. Arab-OSDI, TBUT, and STT used ordinary least-squares regression with HC3 heteroscedasticity-consistent standard errors (SEs); CFS used proportional-odds ordinal logistic regression with HC3 covariance. Sensitivity analyses included median quantile regression for Arab-OSDI, log-transformed TBUT regression, and age-category frequency matching.
Results: Baseline age and sex distributions did not differ significantly between groups (P > 0.05 and P > 0.99, respectively). Mean (standard deviation [SD]) Arab-OSDI score was 17.18 (16.40) in the exposed group and 10.67 (10.53) in controls. After adjustment, exposure was associated with a 6.77-point higher Arab-OSDI score (HC3 SE, 2.96; 95% confidence interval [CI], 0.96 to 12.57; P < 0.05). Associations were not statistically significant for TBUT (regression coefficient [B] = -0.02 s; HC3 SE, 0.71; 95% CI, -1.41 to 1.37; P > 0.05) or STT (B = -0.55 mm; HC3 SE, 2.18; 95% CI, -4.82 to 3.73; P > 0.05). For CFS, the adjusted proportional-odds ratio for a higher staining category was 0.63 (95% CI, 0.18 to 2.18; P > 0.05). Median quantile regression for Arab-OSDI yielded B = 7.05 (95% CI, -0.23 to 14.33; P > 0.05), while regression of log-transformed TBUT yielded a ratio of 1.003 (95% CI, 0.775 to 1.299; P > 0.05). In the frequency-matched subset (N = 68), the adjusted Arab-OSDI difference was 6.82 points (95% CI, 0.09 to 13.56; P < 0.05).
Conclusions: Tobacco smoke exposure was associated with greater dry-eye symptom burden. No statistically significant associations were identified for TBUT, STT, or CFS. Arab-OSDI sensitivity estimates were similar in magnitude and direction, although the median-regression result was not statistically significant. Because exposure pooled cigarette smoking, shisha use, and passive smoke exposure, the findings cannot be interpreted as the isolated effect of active cigarette smoking. Future studies should distinguish these exposure modalities and quantify exposure intensity and duration.

Background: Poor patient cooperation during ophthalmic surgery is demonstrated to result in a variety of complications. The purpose of this study is to evaluate demographic and clinical factors associated with intraoperative patient cooperation during laser in situ keratomileusis (LASIK) surgery.
Methods: This retrospective observational study included patients who underwent LASIK at a single institution. Patients were graded intraoperatively by three observers using a 5-point scale for cooperation during flap creation, fixation during excimer laser ablation, and head/body movement, with lower scores indicating better cooperation. Ordinal regression models were used to evaluate associations between cooperation scores and demographic characteristics or medical history.
Results: A total of 836 patients were included, with a mean age of 35 years (SD, 10.3; range, 18–80 years), 454 (54.3%) male and 382 (45.7%) female; 70% of patients achieved the best overall cooperation score. Patients were significantly less cooperative during flap creation than during head/body movement (P < 0.05). Older age was associated with improved cooperation during flap creation (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96 to 1.00; P < 0.05), laser fixation (OR, 0.97; 95% CI, 0.96 to 0.99; P < 0.05), and movement (OR, 0.97; 95% CI, 0.96 to 0.99; P < 0.05). Female patients displayed significantly better cooperation only during flap creation (OR, 0.71; 95% CI, 0.53 to 0.96; P < 0.05). Longer laser duration was associated with worse cooperation during laser fixation (OR, 1.15; 95% CI, 1.05 to 1.26; P < 0.05) and movement (OR, 1.13; 95% CI, 1.02 to 1.23; P < 0.05). No significant associations were observed between overall cooperation and medical history diagnoses (all P > 0.05); however, anxiety showed an imprecise association with poorer cooperation (OR, 2.20; 95% CI, 0.97 to 5.00).
Conclusions: Patient cooperation during LASIK was generally excellent, although cooperation was worst during flap creation. Older age was modestly associated with improved cooperation across all three categories, female sex was associated only with flap-creation cooperation, and longer excimer laser duration was associated with laser fixation and movement, while no statistically significant associations with the assessed medical-history or medication variables were detected. Prospective studies in LASIK and other refractive procedures are warranted to validate and further elucidate the preliminary findings of this study.

Background: Keratoconus (KC) is a progressive, asymmetric, usually bilateral disorder characterized by central or paracentral corneal thinning. Epidemiological data from the United Arab Emirates (UAE) remain limited. This study estimated the five-year clinic-based period proportion of attendees with recorded KC and described their demographic and clinical characteristics at UAE tertiary eye centers.
Methods: Retrospective cross-sectional study including unique patients aged greater than or equal to 10 years at their first eligible encounter who attended Magrabi Health Centers in Abu Dhabi, Al Ain, or Dubai between January 2020 and December 2024. Unique clinic attendees were identified from electronic medical records; KC cases were identified using a prespecified set of recorded keratoconus diagnosis codes within the ICD-10-CM H18.6 category. Universal systematic KC screening was not conducted for all attendees. The clinical records of KC cases were reviewed for demographic and ocular characteristics. Severity was categorized using a study-specific composite classification informed by selected Amsler–Krumeich and Belin ABCD criteria and based on available keratometric, refractive, pachymetric, and corneal-scarring data.
Results: Among 15,431 unique clinic attendees, 1,027 had recorded KC, corresponding to a five-year clinic-based period proportion of 6.66% (95% CI, 6.27% to 7.06%). The proportion differed significantly by age group, sex, nationality, and location (all P < 0.001). The highest age-specific proportion was observed among the 21–30 age group (14.07%), followed by the 31–40 age group (13.49%). In the exploratory adjusted analysis, compared to attendees aged less than or equal to 20 years the 21–30 age group had the highest adjusted odds ratio (aOR) for recorded KC (aOR = 4.15; 95% CI, 3.34 to 5.15), followed by the 31–40 age group (aOR = 3.85; 95% CI, 3.10 to 4.79). Males (aOR = 1.62; 95% CI, 1.40 to 1.86) and non-Emiratis (aOR = 1.86; 95% CI, 1.63 to 2.13) also had higher adjusted odds of recorded KC. Compared with attendees in Abu Dhabi, those in Al Ain (aOR = 0.46; 95% CI, 0.35 to 0.60) and Dubai (aOR = 0.28; 95% CI, 0.23 to 0.34) had lower adjusted odds. Bilateral involvement occurred in 77.9% (800/1,027) of KC cases. Category I was the most frequent study-specific composite severity category among affected right eyes (54.2%; 499/921) and left eyes (56.8%; 515/906). Corneal scarring was present in 6.7% (62/921) and 7.6% (69/906) of affected right and left eyes, respectively.
Conclusions: The five-year clinic-based period proportion of attendees with recorded KC was 6.66%. Exploratory adjusted analysis suggested that recorded KC is associated with age, sex, nationality, and location. These findings provide clinic-based epidemiological data on KC in the UAE but should not be interpreted as population prevalence.

Background: Posterior capsule opacification (PCO) remains one of the most common late complications following cataract surgery and may lead to decreased visual acuity, glare, contrast sensitivity loss, and impaired visual quality. Nd:YAG laser posterior capsulotomy is currently accepted as the gold standard treatment for symptomatic PCO because of its non-invasive nature and rapid visual rehabilitation. However, despite its widespread use and generally favorable safety profile, concerns remain about procedural variability, postoperative management, and complications such as intraocular pressure elevation, cystoid macular edema, retinal complications, and intraocular lens damage. This updated narrative review aimed to summarize and expand the current evidence on the mechanisms, indications, techniques, outcomes, and complications of Nd:YAG laser posterior capsulotomy.
Methods: A narrative literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science databases, supplemented by Google Scholar screening. The review primarily focused on studies published between 2010 and 2026, although landmark earlier studies were also included when relevant. Primarily English-language publications were included. The search strategy included combinations of the keywords “Nd:YAG capsulotomy”, “posterior capsule opacification”, “photodisruption”, “intraocular pressure”, “retinal detachment”, “cystoid macular edema”, “capsulotomy size”, and “intraocular lens”. Original articles, clinical studies, systematic reviews, meta-analyses, guideline-based publications, and selected case reports were included. Duplicate publications, conference abstracts without accessible full text, and studies with insufficient methodological or clinical information were excluded.
Results: Current evidence demonstrates that Nd:YAG laser capsulotomy provides effective visual rehabilitation in symptomatic PCO and remains a generally safe procedure. Studies evaluating procedural techniques indicate that both cruciate and circular capsulotomy patterns produce comparable visual outcomes, though differences may exist in energy usage, floaters, light scattering, and macular effects. Significant variability persists in clinical practice regarding timing, postoperative medication use, and follow-up protocols. Although most complications are uncommon, clinically important adverse events including retinal detachment, cystoid macular edema, intraocular pressure elevation, inflammation, and intraocular lens pitting have been reported. The risk of certain complications appears to be influenced by patient characteristics, laser energy levels, capsulotomy size, ocular comorbidities, and the interval between cataract surgery and capsulotomy.
Conclusions: Nd:YAG laser posterior capsulotomy remains an effective and reliable treatment for symptomatic PCO; however, important heterogeneity persists regarding procedural approaches and postoperative management. Current evidence suggests that individualized treatment planning, careful patient selection, and conservative energy settings may help minimize complications. Future prospective and standardized studies focusing on visual quality outcomes, patient-reported measures, optimal timing, and complication risk stratification are needed to improve standardization and clinical decision-making in Nd:YAG laser capsulotomy practice.

Background: Acute macular neuroretinopathy (AMN) is a rare but increasingly reported retinal disorder that predominantly affects young women and is characterized by acute-onset paracentral scotomas and distinctive parafoveal macular lesions. Following its first report in 1975 as an inner retinal disease, a considerable body of work has been produced, expanding on its clinical presentation and systemic associations. Aim of this review is to synthesize the current understanding of AMN, including existing controversies on nomenclature.
Methods: A literature search was conducted in PubMed/MEDLINE for English-language articles published up to 31 July 2025. Search terms included “acute macular neuroretinopathy” and “acute macular outer retinopathy”. Additional relevant sources were identified through manual screening of reference lists and targeted updating of the literature through 28 August 2025. Relevant articles were selected for inclusion in this narrative review based on the authors’ judgment of relevance to the review aims.
Results: Multiple cases of AMN in association with a variety of ocular and systemic conditions have been reported. Reported associations include viral illnesses such as influenza, Dengue fever, oral contraceptive use, vasoconstrictive agents, non-ocular trauma, and vaccination. An increased incidence of AMN was reported at a single center during the coronavirus (COVID-19) pandemic. Advances in multimodal retinal imaging, particularly optical coherence tomography (OCT) and OCT angiography, have led to a more precise localization and insight into the pathogenesis of the disease in the outer retinal layers. These findings have prompted some authors to suggest renaming the condition acute macular outer retinopathy (AMOR) to better reflect the anatomical involvement.
Conclusions: AMN appears to primarily affect the outer retinal layers, with current evidence suggesting a role for underlying vascular impairment in its pathogenesis. Although “AMOR” may offer a more anatomically precise description, AMN remains widely used in the academic literature and continues to be both appropriate and accepted. Further research is needed to elucidate the underlying pathophysiology, precisely localize the site of vascular impairment, and explore potential therapeutic strategies. In this context, consistent terminology is essential, and the continued use of the acronym “AMN” is supported by both clinical and historical considerations.

Background: Ocular herpes simplex virus (HSV) disease is uncommon in very young children and may be difficult to recognize because history and examination are limited and early manifestations can resemble bacterial conjunctivitis. Pediatric disease may involve multiple corneal layers, extend into the anterior chamber, recur, and threaten visual development. We describe presumed HSV keratouveitis in a 2-year-old child.
Case Presentation: A 2-year-old girl presented with a two-month history of right-eye pain, photophobia, and tearing after an episode diagnosed elsewhere as HSV blepharoconjunctivitis. Previous topical treatments, including antibiotics, had produced little improvement. Examination revealed right eyelid edema, conjunctival congestion, and an inferior geographic epithelial defect involving one-third of the cornea; the anterior chamber was quiet. Suspected HSV epithelial keratitis was treated with topical acyclovir 3% ointment, moxifloxacin, and lubrication. Although the epithelium healed, stromal edema, infiltration, and endotheliitis developed. Topical prednisolone acetate and therapeutic-dose oral acyclovir were commenced after normal renal function was confirmed. Serological testing showed reactive cytomegalovirus (CMV) IgG and IgM; Epstein-Barr virus IgG and IgM, HSV-1 IgG, HSV-2 IgG, rubella IgM, and Toxoplasma IgG and IgM were non-reactive. Initial improvement was followed by acute recurrence one week after transition to prophylactic acyclovir. Examination under anesthesia revealed a recurrent 3-mm epithelial defect, diffuse stromal edema and infiltration, 2+ anterior chamber cells, and right-eye intraocular pressure of 29 mmHg; no keratic precipitates, iris atrophy, synechiae, or posterior-segment abnormalities were identified. Ocular-surface HSV-1/HSV-2 polymerase chain reaction (PCR), obtained after four weeks of topical and three weeks of systemic acyclovir, was negative, and bacterial cultures showed no growth. Ocular CMV and varicella-zoster virus testing was not performed, and the parents declined aqueous-humor sampling. The child received intravenous acyclovir (10 mg/kg every 8 hours) and methylprednisolone (1 mg/kg/day) for five days, with topical anti-inflammatory, cycloplegic, pressure-lowering, lubricating, and initially empirical antibacterial treatment. At discharge, the eye was quiet, intraocular pressure had normalized, and a 4-mm paracentral stromal opacity remained. At six months there was no recurrence; intraocular pressure was 15 mmHg, refraction was stable, and no fixation preference or ocular misalignment was observed.
Conclusions: The sequential unilateral epithelial, stromal, endothelial, and anterior uveal involvement favored HSV, but absent aqueous-humor testing and negative post-treatment surface PCR precluded virological confirmation. This case supports longitudinal assessment of persistent unilateral corneal inflammation in young children and surveillance for recurrence, corneal sequelae, and impaired visual development.

Background: Compulsory service programs are used to improve access to health professionals in underserved areas. Their implementation depends on workforce conditions, organizational support, and the wider policy environment. Specialist services such as ophthalmology likewise rely on functioning clinical infrastructure, trained support staff, and referral capacity. This study aimed to identify the main factors and driving forces shaping the future of Iran’s compulsory service program for healthcare workers in underserved areas, drawing on ophthalmologists’ experiences and an expert-panel assessment.
Methods: A qualitative driver-analysis study was conducted. Environmental scanning drew on articles, books, media sources, and expert interviews. Eighteen ophthalmologists were interviewed using purposive sampling, with recruitment continuing until code saturation was reached. Interview data were analyzed using conventional qualitative content analysis, and the identified factors were subsequently organized using the PESTEL framework: political, economic, sociocultural, technological, environmental, and legal factors. A five-member expert panel identified the final driving forces qualitatively through discussion.
Results: Eighteen ophthalmologists participated in the interviews: 13 (72.2%) were men, median age was 37.5 years (IQR, 35.0–42.8; range, 30–63), and 12 (66.7%) had personally worked in an underserved area. Responses on the principal challenge were categorized as financial for 10 participants (55.6%), management or implementation for seven (38.9%), and sociocultural for one (5.6%); 17 participants (94.4%) considered the program in need of redesign, and 13 (72.2%) stated they would be willing to serve in an underserved area if major problems were corrected. The expert panel identified 10 driving forces: national infrastructure development; welfare and financial support for the health workforce; international sanctions; service-recipient satisfaction; willingness of policymakers, legislators, and implementers to continue the program; political and social stability and security; social demand for free medical services; epidemics and emerging diseases; physicians’ social satisfaction; and the national health profile, including population and disease patterns.
Conclusions: In this purposively selected ophthalmologist sample, financial and management or implementation problems were the most frequently categorized immediate challenges. The expert panel identified 10 driving forces spanning workforce conditions and broader political, social, and health-system factors. These driving forces should be regarded as expert-identified areas for policy review and future evaluation rather than as established causal determinants.